Flashcards in Biochem contd step 17-30 Deck (50):
A palindromic sequence in DNA occurs when reading the nucleic acids in the 5' to 3' direction on one strand matches reading the nucleic acids on the complimentary strand in the other direction. In this case, the complementary strand of?
5' TGTACA 3' is 3' ACATGT 5'. Reversing that strand would read 5' TGTACA 3', which is identical to the original strand. This is a true DNA palindromic sequence.
The boy presents with signs (increased creatinine, hematuria) and symptoms (lower back and pelvic pain) consistent with ?
2.Microscopic evaluation of the stone is an important key to identifying the cause. A hexagonal shaped microscopic crystal is characteristic of ?
nephrolithiasis. This condition is relatively uncommon in children and hereditary causes should be investigated in young patients with recurrent kidney stones.
2.cystinuria. Patients with cystinuria typically have increased levels of lysine and arginine in their urine due to a defect in amino acid reabsorption in the proximal tubule which leads to wasting of lysine, arginine, cystine, and ornithine.
The elevated cystine level in the urine leads to recurrent stone formation. Treatment involves hydration and alkalization of the urine with acetazolamide.
Although hyperparathyroidism can be a cause of recurrent nephrolithiasis,?
it would not cause elevated lysine and arginine levels in the urine
Hyperparathyroidism could cause nephrolithiasis,?
but not elevated arginine and lysine levels in the urine.
A defect in the vitamin D receptor would not cause ?
elevated arginine and lysine levels in the urine.
This patient, who has an occupational exposure to heavy metals, presents with symptoms of fatigue and headache. His history and clinical presentation, as well as the basophilic stippling (shown by the arrows in the vignette image), point toward a diagnosis of ?
lead poisoning. Lead can cause demyelination and degeneration of axons, which explains the peripheral neuropathy (“wrist drop” finding on exam). In chronic lead poisoning, the anemia is due to a lack of functional hemoglobin. Lead inhibits synthesis of heme on two levels: (1) It blocks δ-aminolevulinic acid dehydratase, and (2) it decreases iron incorporation into heme. Without heme, the hemoglobin molecule cannot function. Inherited defects of the same biochemical pathway responsible for this patient's symptoms can result in acute intermittent porphyria, producing abdominal pain and psychological disturbances, as well as porphyria cutanea tarda, characterized by photosensitivity.
An increase in the fetal form of hemoglobin (HbF) would not be expected, since?
defects in the heme synthesis pathway would affect HbF the same as it affects HbA (adult hemoglobin), as heme and globin pairing would be universally affected.
A defect in heme synthesis would not result in?
increased heme breakdown products, making jaundice and splenomegaly unlikely.
A defect in the heme synthesis pathway would result in decreased levels of hemoglobin in RBCs, but would not produce ?
a buildup of oxygenated hemoglobin. In fact, the level of oxygenated vs. deoxygenated hemoglobin would not be altered
A decrease in hemoglobin’s affinity for oxygen binding would not result from a?
defect in the heme synthesis pathway. A microcytic anemia would be more likely.
The patient’s presentation of orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema are highly suggestive of ?
congestive heart failure (CHF). His recent symptoms, including nausea, vomiting, and visual changes, are likely related to digoxin toxicity. Digoxin (although not first-line therapy) is one treatment option for CHF, and it works by increasing contractility and thus cardiac function.
Digoxin inhibits the Na+/K+ pump, which typically extrudes three Na+ for every two K+ brought into the cell during depolarization. Because the pump is inhibited, the intracellular concentration of Na+ increases
Digoxin’s mechanism of action does not directly affect ?
intracellular levels of bicarbonate, magnesium, chloride, or hydrogen.
This drug acts during the metaphase of the cell cycle and disrupts the function of the mitotic spindle. This description is consistent with the mechanism of action of ?
paclitaxel, a chemotherapeutic agent that prevents microtubule depolymerization, thereby stabilizing the mitotic spindle and preventing the migration of chromatids to their respective ends of the cell. Mitosis remains incomplete, leading to cell death. Paclitaxel is primarily used to treat advanced ovarian cancer and metastatic breast cancer.
5-fluorouracil resembles a nucleotide and therefore arrests the cell in? synthesis
the S phase, inhibiting DNA
Bleomycin intercalates DNA and causes ?
reactive oxidative species damage in the G2 phase
Cyclophosphamide alkylates DNA strands together, resulting in ?
crosslinking and impairing cell division throughout the entire cell cycle.
vincristine arrests cells in metaphase, it prevents ?
microtubule aggregation, a mechanism of action opposite to that of taxanes like paclitaxel.
This patient has a positive Gower sign—use of the upper extremities to stand up. When combined with his calf pseudohypertrophy (large muscle size in the presence of diminished muscle strength), the patient most likely has ?
the X-linked disorder, Duchenne muscular dystrophy (DMD).
DMD is caused by deletion of one or more exons of the DMD gene, which encodes the dystrophin protein; the exon deletion results in truncated and inactive dystrophin. Dystrophin plays a critical structural role by linking the cytoskeleton of the myocyte with the extracellular matrix. Its absence ultimately results in diminished muscle strength caused by progressive myofiber damage. Eventually, the muscle fibers are replaced with fat cells, which explains the large calves seen in patients with DMD.
Frameshift mutations are the most common cause of DMD. The other types of mutations are not the most likely cause of DMD.
Nonsense mutations are involved in about 10% of genetic diseases, including cases of DMD, cystic fibrosis, and spinal muscular atrophy. However, ?
frameshift mutations, rather than nonsense mutations, are more likely to cause DMD.
Nonstop mutations are associated with an array of ?
congenital diseases, including mitochondrial neurogastrointestinal encephalomyopathy and variable anterior segment dysgenesis.
Splice site mutations are a rare cause of?
cancers, dementia, epilepsy, and some types of β-thalassemia.
Missense mutations may result in? .
sickle cell disease because of a substitution of glutamic acid with valine
A 2-year-old boy has a fever; green, malodorous nasal discharge; and tender facial sinuses, most likely secondary to a sinus infection. He also has a history of multiple similar infections and physical exam findings that indicate his heart is on the right side of the chest (dextrocardia), which is confirmed by the chest x-ray. The combination of these symptoms is characteristic of ?
Kartagener syndrome or primary ciliary dyskinesia (PCD), a congenital (autosomal recessive) impairment of mucociliary clearance that is caused by a defect in dynein that prevents effective movement of cilia.
Cilia move by sliding their dynein microtubules to cause bending of the radial spokes within their structure. Kartagener syndrome is caused by a ?
defect in dynein that prevents effective movement of cilia. It is characterized by sinusitis, bronchiectasis, situs inversus, and male and female infertility.
Defective chloride transport occurs in patients with ?
cystic fibrosis and is associated with chronic respiratory infections but not with situs inversus
Elevated blood sugar is found in patients with diabetes and can cause chronic infections but is unlikely to be diagnosed ?
at this age and is not associated with situs inversus.
Kyphoscoliosis is a spinal column abnormality that is more commonly associated with?
Tetralogy of fallot is a congenital cyanotic heart defect that is not associated with ?
chronic respiratory infections or situs inversus.
The patient is a young black girl with a history of anemia who experiences recurrent severe pain in her right hip and back. With no other lab values or other diagnostic tests mentioned in the vignette, you can assume that the USMLE expects you to recognize the symptoms of a ?
sickle cell crisis.
In low concentrations, HbS has the same oxygen-hemoglobin dissociation curve as normal hemoglobin, or hemoglobin A (HbA). HbS also has the same oxygen-hemoglobin dissociation curve as HbA at high PO2. During a crisis, however, deoxygenated HbS forms a polymer that has ?
less affinity for oxygen, and the curve is shifted to the right. This facilitates unloading of oxygen to tissues and is reflected by curve D in the image.
Other conditions that shift the oxygen-hemoglobin dissociation curve to the right include?
increased metabolism (ie, increases in temperature, carbon dioxide, and hydrogen ions in tissue), increased 2,3-bisphosphoglycerate (2,3-BPG), and high altitude.
This patient with a dislocated lens associated with vision difficulties, taller than average stature, and scoliosis, shows signs and symptoms of ?
Marfan syndrome, a connective tissue disorder.
Together with ectopia lentis (a displaced lens), aortic involvement is a primary hallmark of Marfan syndrome and may be manifest with dilation of the aortic root leading to aortic regurgitation that is detectable on auscultation as a decrescendo diastolic murmur. Aortic dissection and mitral valve prolapse may also be seen.
Marfan syndrome is caused by a ?
mutation of the fibrillin gene, located on chromosome 15. Fibrillin is one of the major components of microfibrils, which are essential to the formation of elastin in the aorta, suspensory ligaments of the lens of the eye, and other connective tissues. Decreased microfibril formation results in the release of excessive growth factor and decreased elasticity in many tissues.
Venous thrombosis is not caused by?
any connective tissue disease.
Marfan syndrome causes dilation in?
the aorta instead of aortic stenosis (narrowing of the lumen)
Ischemic strokes are often due to plaques in the vessels, which are not associated with?
2. Primary hypertension may be?
2. genetic in origin, but is also not associated specifically with connective tissue disease.
Steroid hormones enter cells and bind to receptor proteins. The receptor-hormone complex binds to ?
specific response elements, or the regulatory region of DNA, and activates gene transcription.
A ruptured aortic aneurysm in a man of this patient's age suggests the presence of an underlying disorder. Aortic aneurysms (both abdominal and thoracic) can be sequelae of ?
Ehlers-Danlos syndrome (EDS), a group of genetic disorders characterized by joint hypermobility, skin hyperelasticity, joint laxity, easy bruising, and tissue weakness.
The most common type of EDS is the hypermobility type, which is not associated with a known single collagen-type deficiency. However, a defect in the synthesis of type III collagen is the most frequently seen defect in the vascular type of EDS, as seen in this patient. In the vascular form of EDS, skin hyperelasticity is less prominent. Instead, patients often exhibit thin or transparent skin and increased varicosity.
1. A defect in elastin synthesis results in ?
2. Mutations in fibrillin lead to ?
3.The synthesis of type I collagen is defective in a?
4. Defective synthesis of type IV collagen is?
an increase in tissue rigidity rather than an increase in elasticity, as seen in this patient.
2. Marfan syndrome.
3. spectrum of disorders known as osteogenesis imperfecta (brittle bone disease).
4. present in Alport syndrome.
The experimental drug inhibits the duplication of double-stranded DNA in tumor cells. Replication of cellular DNA occurs during?
2. he S phase is the cell cycle phase during which?
the S phase. If there were a break in the DNA during this phase, the cell would not be able to replicate until the break is repaired. But if the break is irreparable, the cell would undergo apoptosis, or programmed cell
2. DNA is synthesized, and drugs such as antimetabolites (mercaptopurine, 5-fluorouracil, methotrexate) interfere with this process.
G2 is the pre-mitotic growth phase and is marked by?
RNA and protein synthesis. Damage to DNA in this phase will not cause a cell to undergo apoptosis.
G1 is the postmitotic growth phase and is marked by?
the synthesis of proteins involved in DNA synthesis. But damage to DNA will not cause a cell in G1 phase to undergo apoptosis.
During G0, cells are in the quiescent stage and are not actively replicating their DNA or dividing. Thus, ?
the experimental drug would not have an effect on G0 cells.
During the M phase, the diploid chromosomes align along the metaphase plate and migrate to?
the mitotic poles and cytokinesis begins. Because DNA replication has already occurred, the experimental drug will not have any effect during M stage.
The disease in the question stem is Duchenne muscular dystrophy. This is caused by an X-linked frameshift mutation and results in ?
accelerated muscle breakdown. Calf muscles become enlarged due to fatty replacement of muscle, called calf pseudohypertrophy. Hemophilia A and B are inherited in the same manner.
Cystic fibrosis is an ?
2. Hemochromatosis is caused by ?
1. autosomal recessive disorder
2. abnormally high storage of iron. It is an autosomal recessive disorder.
1. Marfan syndrome has an autosomal dominant inheritance pattern. It is caused by a ?
Neurofibromatosis types 1 and 2 share an autosomal dominant inheritance pattern. This disorder is characterized by?
mutation in fibrillin and results in tall individuals with long extremities; pectus excavatum; hyperextensible joints; long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of the aorta; and a floppy mitral valve.
2. café-au-lait spots, neural tumors, and Lisch's nodules.
This patient presenting with hemoptysis and hematuria in the setting of elevated creatinine and BUN illustrates the classic picture of?
Goodpasture syndrome. Goodpasture syndrome is an autoimmune disorder in which the body produces immunoglobulins against the α3 chain found in type IV collagen—a structural component of the basement membrane of pulmonary alveoli and renal glomeruli. This is an example of a type II hypersensitivity reaction.
Patients with Goodpasture syndrome are typically young men with an onset of fatigue, pulmonary symptoms including dyspnea and hemoptysis, and renal symptoms such as dysuria, hematuria, and renal failure. A CT scan is routinely obtained to evaluate hemoptysis. The CT scan shown here is a good example of the pulmonary manifestations of Goodpasture syndrome, and shows patchy opacity (groundglass opacity) in both the upper lobes and apical lower lobes of both lungs. Alport syndrome is characterized by?
defective type IV collagen. Alport syndrome is a hereditary form of glomerulonephritis with sensorineural hearing loss and, sometimes, ocular abnormalities. The disease arises from a mutation in one of the α chains of type IV collagen: α3, α4, or α5.